Hypersensitivity reactions

What happens when the immune
system doesn’t work the way it
should??

1

What makes us sick?

 “enemies” in the environment in the form of
microbes and chemicals are constantly
attacking our bodies, disrupting homeostasis

 sometimes immune system homeostasis is
disrupted on its own

it may over-react to
antigens such as
with allergies
 it may react to self
proteins as with
autoimmune disease
it may under-react as
with human
immunodeficiency
virus infection (HIV) 2

Over-reaction to antigens

Pollen grains Mast cell

©Dennis Kunkel Microscopy, Inc., www.DennisKunkel.com

•the immune system reacts to antigens (allergens) that don’t
cause a reaction in most people – like pollen

4

Over-reaction to antigens
 a type of antibody called IgE binds to the allergen
causing mast cells to produce chemicals called
histamines.
 Common symptoms include:
 runny nose and itchy, watery eyes, with repeated exposure
resulting in a more rapid onset of symptoms
 treatments
 antihistamines are given to counteract the histamines
 shots containing low doses of an allergen can help a person to
become desensitized to that specific antigen

5

Disorders of the immune system

1. Allergy
2. Autoimmune disease
3. Immunodeficiency

 The immune system is an integral part of human
protection against disease, but the normally
protective immune mechanisms can sometimes
cause detrimental reactions in the host.
 Such reactions are known as hypersensitivity
reactions, and the study of these is termed
immunopathology.

 The traditional classification for hypersensitivity
reactions is that of Gell and Coombs and is
currently the most commonly known
classification system.
 It divides the hypersensitivity reactions into the
following 4 types:

 Type I reactions
 Immediate hypersensitivity reactions
 Type II reactions
 Cytotoxic hypersensitivity reactions
 Type III reactions
 Immune-complex reactions
 Type IV reactions
 Delayed hypersensitivity reactions, cell-mediated
immunity

 Type I reactions
 involve immunoglobulin E (IgE)–mediated release of histamine and other mediators
from mast cells and basophils.
 Type II reactions
 involve immunoglobulin G or immunoglobulin M antibodies bound to cell surface
antigens, with subsequent complement fixation.
 Type III reactions
 involve circulating antigen-antibody immune complexes that deposit in postcapillary
venules, with subsequent complement fixation.
 Type IV reactions
 mediated by T cells rather than by antibodies.

 Some authors believe this classification system may be
too general and favor a more recent classification
system proposed by Sell et al.
 This system divides immunopathologic responses into
the following 7 categories:
1. Inactivation/activation antibody reactions
2. Cytotoxic or cytolytic antibody reactions
3. Immune-complex reactions
4. Allergic reactions
5. T-cell cytotoxic reactions
6. Delayed hypersensitivity reactions
7. Granulomatous reactions

Hypersensitivity reaction
 undesirable side effect of immunity manifesting trivial
discomforts such as itching of the skin to potentially fatal
disease such as bronchial asthma.
 initiated by the interaction of antigen w/ humoral antibody
or by cell-mediated immune mechanisms.

Type I. Anaphylactic Type

Type II. Cytotoxic Type

Type III. Immune Complex-Mediated

Type IV. Cell-Mediated

Type V. Stimulatory Reactions

Hypersensitivity
There are four different types of hypersensitivities that
result from different responses of the immune
system:
Type I: Immediate hypersensitivity
- onset within minutes of antigen challenge
- examples are allergies to molds, insect bites
Type II: Cytotoxic hypersensitivity
- onset within minutes or a few hours of antigen challenge
- examples are adult hemolytic anemia and drug allergies

Type III: Immune complex-mediated hypersensitivity
- onset usually within 2-6 hours
- examples include serum sickness and systemic lupus
erythematosus
Type IV: Delayed Hypersensitivity
14
- inflammation by 2-6 hours; peaks by 24-48 hours

Process of Allergy
 Step 1: Sensitization
 Occurs when one develops IgE antibodies against a
substance that is inhaled, ingested, or injected
 Newly formed IgE antibodies stick to basophils and
mast cells no s/s yet
 Step 2: Reexposure to allergen
 (+) s/s
 Cellular events for all immediate allergic reactions is
the same

 Reexposure to the antigen can then result in the
antigen binding to and cross-linking the bound
IgE antibodies on the mast cells and basophils.
 This causes the release and formation of
chemical mediators from these cells.
 These mediators include
 preformed mediators,
 newly synthesized mediators,
 cytokines

Type I:
Immediate hypersensitivity

Type I. Immediate Hypersensitivity
Reactions
 rapidly developing immunologic reaction
occurring w/in minutes after the combination of
an antigen w/ antibody bound to mast cells or
basophils in individuals previously sensitized to
the antigen.
 may occur as a systemic or as a local reaction.

Etiology
 Allergic reactions
 Reactions can be elicited by various aeroallergens
(eg, pollen, animal dander), drugs, or insect stings.
 Other possible causes are latex, drug, and food
allergy.

Biological basis allergies

histamine

Etiology
 Allergens
 Allergens can be complete protein antigens or low–molecular-
weight proteins capable of eliciting an IgE response.
 Pollen and animal dander represent complete protein antigens.
 Haptens are low–molecular-weight (inorganic) antigens that are
not capable of eliciting an allergic response by themselves.
 must bind to serum or tissue proteins in order to elicit a response.
 a typical cause of drug hypersensitivity reactions.
 Note that all drug hypersensitivity reactions are not mediated by IgE.
 In addition to anaphylactoid reactions, drug reactions can be caused by
cytotoxicity and immune-complex formation and by other immunopathologic
mechanisms.

Etiology
 Foods
 most common food allergens are
 peanuts, tree nuts, finned fish, shellfish, eggs, milk, soy, and
wheat.
 Certain foods can cross-react with latex allergens.
 These foods include banana, kiwi, chestnut, avocado,
pineapple, passion fruit, apricot, and grape.

Etiology
 Hymenoptera
 Bee, wasp, yellow jacket, hornet, and fire ant stings
can cause IgE-mediated reactions.
 While anaphylaxis is the most serious reaction,
localized swelling and inflammation can also occur
and do not by themselves indicate increased risk of a
subsequent life-threatening reaction.
 At least 50 Americans die each year from anaphylaxis
caused by a stinging insect.

Systemic reaction
 usually IV injection of an antigen to which the
host has already become sensitized
  state of shock can be produced within
minutes (may be fatal)

Local reactions
 depend on the portal of entry of the allergen.
May take the form of:
 localized cutaneous swelling (skin allergy,
hives)
 nasal & conjunctival discharge (allergic rhinitis
and conjunctivitis)
 hay fever
 bronchial asthma
 allergic gastroenteritis (food allergy)

Type I hypersensitivity – sensitization to an inhaled
allergen or bee sting

cytokines

 

Mast
cell

Antigens (red dots) from inhaled pollen are ingested and presented by
macrophages to T cells. Activated T cells produce cytokines leading to
the production of IgE, which binds to receptors on mast cells and causes
the release of histamine, which is responsible for allergy symptoms.
Onset is usually within minutes of contact with antigen.
27

Initial response

•vasodilation
•vascular leakage
•smooth muscle spasms

Allergens stimulate immune system cells to Late phase reaction
make antibodies and chemical signals (such as
histamine) to induce inflammation •mucosal edema
•mucus secretion
•leukocyte infiltration
•epithelial damage
•bronchospasm

Allergy is characterized by a local or
systemic inflammatory response to allergens
Local symptoms:
 Nose: swelling of the nasal mucosa (allergic rhinitis)
 Eyes: redness and itching of the conjunctiva (allergic conjunctivitis)
 Airways: bronchoconstriction, wheezing, sometimes outright attacks of
asthma
 Ears: feeling of fullness, possibly pain, and impaired hearing due to the lack
of eustachian tube drainage.
 Skin: various rashes, such as eczema, hives and contact dermatitis.
 Head: while not as common, headaches are seen in some with
environmental or chemical allergies.

Systemic allergic response
 Is also called anaphylaxis
 Depending of the rate of severity, it can cause cutaneous reactions,
bronchoconstriction, edema, hypotension, coma and even death.

Allergen

IgE production by B lymphocytes
(at the site of entry of antigen & draining LNs)

IgE antibodies attach to mast cells and
basophils

The person is sensitized to that allergen.
Memory cells are generated.

Re-exposure to the allergen

Binding of allergen to 2 adjacent IgE
molecules on the surface of a basophil or
mast cell

Destortion of the cell membrane
causing them to degranulate

Release of vasoactive amines (histamine)
into the circulation.

Histamine

Increased capillary Increased mucus Pruritus and
permeability secretion erythema

Edema, facial Watery nasal and
puffiness conjunctival discharge

Primary Phase

Secretion of leukotrienes and
prostaglandins

Stimulation of more WBC

Generalized inflammatory reaction

Secondary Phase

Laboratory
• CBC
– Increased WBC – eosinophil
count
• Increased serum IgE levels
– Normal values 39IU/ml
– Does not determine indicate
specific antigen
• Radioallergosorbent Test
(RAST)
– Determines the blood
concentration of IgE directed
against a specific antigen and
thus can determine specific
antigen

Allergy testing
 Scratch test
 Intradermal test
 Oral food challenge
 In vitro testing

Allergy Testing
 Skin Testing
 Scratch Test
 Results in an immediate hypersensitivity reaction to an
allergen
 Discontinue antihistamines for 5 days before the test
 Allergens are introduced through a superficial scratch or prick
cause a localized reaction (wheal) when the test result is
positive
 Serious reactions are rare

Skin test
 The allergens are either injected intradermally or into small
scratchings made into the patient's skin
 If the patient is allergic to the substance, then a visible inflammatory
reaction will usually occur within 30 minutes.
 This response will range from slight reddening of the skin to full-blown
hives in extremely sensitive patients.

 Problems: some people may display a delayed-type hypersensitivity
(DTH) reaction which can occur as far as 6 hours after application of the
allergen and last up to 24 hours. This can also cause serious long-lasting
tissue damage to the affected area. These types of serious reactions are quite
rare.

 Wash the solution from the skin
 Topical steroids and oral antihistamines are
administered to reduce itching ( sedation)

 Intradermal Testing
 Reserved for substances that are strongly suspected
of causing allergy but did not test positive during
scratch test
 Greater risk for anaphylaxis occurs

 Oral Food Challenge
 Effective for some individuals in identifying specific
allergens when skin testing has been inconclusive
 Eliminate suspected foods for 7-14 days before
testing
 Eat a defined food for at least one day and monitor
clients reaction

In Vitro Testing
• Drawing blood from a
client and exposing it to
different panels containing
food and mold allergens
• After incubation the cells
are checked
• Positive reaction
– Increase WBC size by 12 %
– Increased platelet
aggregation

Collaborative Management

• Avoidance
Therapy

Medications
 Decongestants
 vasoconstriction in the inflamed tissue thereby
reducing the edema
 Caution in patients with HPN, glaucoma
 Antihistamines
 blocks histamine from binding with its receptor
preventing vasodilation and capillary permeability
 Sedation

 Corticosteroids
 decrease inflammation by preventing the synthesis of
mediators
 Nasal
 Beclomethasone
 Fluticasone
 Oral
 Prednisolone
 Prednisone

 Mast Cell Stabilizers
 Prevent mast cell membranes from opening when
allergen binds to IgE
 Cromolyn sodium
 Leukotriene Inhibitors
 Zileuton
 Zafirlukast

Desensitization
 The most common form of desensitization
involves subcutaneous injections of small
amount of the allergen
 An increasing dose is usually given weekly until
the patient is receiving a 0.5ml dose
 Recommended course of treatment is
approximately 5 years

Desensitization
 The mechanism of action to reduce allergic
responses by desensitization is thought to be
competition.
 Instead of IgE , IgG is produced and binds with
the allergens so as not to cause degranulation of
mast cells or basophils.

 Desensitization has been effective for a few antigens, particularly
bee venom.
 This type of treatment is designed to cause an IgG response instead
of an IgE response.
 The allergen is either ingested or injected into the subject starting in
small amounts and increased to larger amounts. This treatment can
have 2 effects:
 T-helper 1 cells produce more IgG which binds to the antigen so that
it can’t bind to IgE receptors on mast cells and cause release of
histamines.
 2) IgG binds to and removes the antigen before it binds to T-helper
2 cells. The T- helper 2 cells will then not be able to produce the B
cells that will produce IgE.

Allergic rhinoconjunctivitis
s/s
 Congestion
 Sneezing
 Itchy , runny nose and eyes;
 Itching of the palate and inner ear.
 postnasal drip, which can cause sore throat,
coughing, or throat clearing.

Rhinoconjunctivitis
 usually results from exposure to aeroallergens
 can be seasonal or perennial.
 Airborne allergens typically also cause ocular
symptoms consisting of itchy eyes, tearing,
swelling or redness of the eyes.
 Repeated exposure to the allergen can result in
chronic allergic inflammation, which causes
chronic nasal congestion that can be further
complicated by sinusitis.

s/s
 Patients may sneeze, be congested, have a runny nose,
or have frequent throat clearing and/or cough from
postnasal drip.
 Sclera may be injected, and patients may have dark
rings under the eyes (ie, allergic shiners).
 Nasal mucosa can be boggy and pale, usually with clear
drainage.
 The pharynx may have a cobblestone appearance
reflecting lymphoid hyperplasia from postnasal mucus
drainage.
 The patient may have frontal or maxillary sinus
tenderness from chronic sinus congestion or infection.

Additional Diagnostic test
 Nasal smear tests
 look for eosinophils.
 However, regular use of a nasal corticosteroid can lower the eosinophil
count.
 Elevated eosinophil levels can be consistent with allergic rhinitis.

Mgmt
 Avoid the offending allergen, if possible.
 Oral H1-receptor blockers
 helpful for controlling itchiness, rhinorrhea, and
lacrimation but most have little effect on nasal
congestion.
 intranasal glucocorticosteroid
 control nasal symptoms, including nasal congestion.
 need to be used regularly to be effective
 patients may need to use them for a week or more
before maximum effect is seen.

Mgmt
 Other topical nasal agents include
 azelastine
 olopatadine (H1-receptor blockers)
 cromolyn (a mast cell stabilizer).
 Nasal antihistamines have a rapid onset of
action and can be used on an as-needed basis.

Mgmt
 Topical nasal decongestants can provide
immediate relief of nasal congestion and can be
used temporarily and as needed.
 Note: Patients should be cautioned not to use
them for more than a few days, however, as they
can cause rebound congestion (rhinitis
medicamentosa).

Mgmt
 ocular symptoms
 Topical decongestants, mast cell stabilizers, or
antihistamines
 artificial tears - can be refrigerated for an extra
cooling effect.
 Cold compresses can also be used.
 Note: use of topical decongestants should be
limited to a few days, as longer use can result in
rebound vasodilation.

Antigen-injection immunotherapy
 AKA: subcutaneous immunotherapy (SCIT)
 very effective in treating inhalant allergies and
can be considered in patients whose symptoms
do not respond well to medications or in patients
who cannot avoid the allergen in question (eg,
cat owner allergic to cats).
 The mechanism of action of immunotherapy is
not yet fully elucidated.

Sublingual/swallow immunotherapy
(SLIT)
 An alternative to antigen-injection immunotherapy
 currently being used with increasing frequency in
Europe.
 involves having the patient hold extract under the tongue
for 1-3 minutes before swallowing.
 It offers the advantage of a lower likelihood of systemic
adverse effects and has been shown to reduce allergic
rhinitis and asthma symptoms.
 may have a more significant impact on these symptoms
than SLIT.
 still being evaluated for FDA approval in the United
States.

Allergic asthma
s/s
 Bronchoconstriction
 shortness of breath (eg, difficulty getting air out),
wheezing, cough, and/or chest tightness.

 Long-term allergen exposure can cause
 chronic changes of increased difficulty breathing and
 chest tightness
 and the patient may give a history of repeated rescue
inhaler use or reduced peak flows.

 Patients may be coughing or appear short of
breath.
 Wheezing may be present, but it might not be
heard in patients with milder symptoms or, if the
asthma is very severe, patients may not move
enough air to produce wheezing.
 Breaths may be shallow or the patient may have
a prolonged expiratory phase.
 Cyanosis of the lips, fingers, or toes (caused by
hypoxemia) may occur with severe asthma.

Additional diagnostic tests
 Spirometry/pulmonary function tests
 Spirometry or pulmonary function tests offer an objective means of assessing
asthma.
 Peak-flow meters can also be used for this and can be used by patients at home
to monitor their status.
 Inhalation challenge with histamine, methacholine, and specific
allergen
 confirm airway hypersensitivity or allergen sensitivity.
 Measurement of exhaled nitric oxide
 used to evaluate inflammation in the airways seen with asthma and to follow
efficacy of or adherence to anti-inflammatory medications (eg, inhaled
corticosteroids).
 Induced sputum:
 Sputum induced from the airways can be evaluated for eosinophils, which is a
measure of inflammation seen in asthma.

Mgmt
 Avoid the offending allergen, if possible.
 A key factor in controlling allergic asthma is
controlling allergic rhinitis symptoms.

Mgmt
 Therapy depends on the severity of disease.
 albuterol metered-dose inhaler (MDI) (or
nebulizers for young children) to use as needed.
 Inhaled glucocorticosteroids should be added if
appropriate.
 In general, these medications are used if
symptoms occur more than twice weekly or if
abnormal spirometry findings reverse with the
inhalation of a short-acting bronchodilator.
 .

Mgmt
 For more refractory symptoms
 long-acting beta agonist may be added to the inhaled
glucocorticoid
 Leukotriene inhibitors can also be added.
 Systemic corticosteroid bursts may need to be
used for exacerbations of severe cases.
 Patients with allergic asthma may respond well
to specific allergen immunotherapy.

Mgmt
 omalizumab (Xolair)
 a humanized monoclonal antibody that prevents
binding of IgE to high-affinity IgE receptors on mast
cells and basophils
 In patients refractory to the usual medications and
who have antigen-specific IgE to perennial
environmental aeroallergens (positive skin test or
RAST result)

Urticaria/angioedema
s/s
 Diffuse hives or wheals may occur and cause significant
pruritus;
 individual wheals resolve after minutes to hours, but new
wheals can continue to form.
 Acute urticaria (lasting < 6 wk) can be caused by viral
infections, foods, drugs, or contact allergens.
 Chronic urticaria lasts longer than 6 weeks. Although
many causes are possible, often, a cause is not found. In
many cases, this is not due to antigen-IgE – mediated
immediate hypersensitivity but to an autoantibody to the
high affinity IgE receptor or to IgE itself.

 (+) wheals with surrounding erythema.
 Wheals from allergic causes usually last a few
minutes to a few hours.
 Wheals due to cutaneous vasculitis may last more
than 24 hours and may leave postinflammatory
hyperpigmentation upon healing.

 Angioedema
 is localized tissue swelling that can occur in soft
tissues throughout the body.
 pain at the site of swelling instead of pruritus, which
occurs with urticaria.
 particularly concerning if pharyngeal or laryngeal
tissues are involved.
 Angioedema of the laryngopharynx
 can obstruct the airway; difficulty breathing.
 Stridor or hoarseness
 can be life threatening.

Mgmt
 Avoid the offending allergen if known.
 H1-receptor blocker should be added.
 If symptoms are not controlled with this alone,
 an H2-receptor blocker, leukotriene inhibitor, or oral
glucocorticosteroid can be added.
 Most patients require higher than the usual doses;
 employing twice daily H1 and H2 antihistamines for
successful control is not uncommon.

Atopic dermatitis
 is an eczematous cutaneous eruption more
common in children than in adults;
 can be exacerbated by allergen exposure,
especially food allergies
 (+) pruritus which produces the lesions.
 Superinfection with staphylococcal organisms can
occur, particularly in severely excoriated or cracked
lesions.

 physical examination findings can vary with the
severity of the disease.
 less severe cases - skin can appear normal, dry, or
with erythematous papules.
 more severe cases - patients can have extremely dry,
lichenified, cracked, and, sometimes, crusted lesions.
 In infants, the head and extensor surfaces are
more involved, whereas in older children and
adults, the flexural surfaces tend to be affected.

Mgmt
 Avoid the offending allergen if possible, and
properly hydrate and care for the skin.
 Topical glucocorticosteroids and topical
immunomodulators (eg, tacrolimus) can be
used.

Anaphylaxis
 Most dramatic and life-threatening
 Occurs rapidly and systematically
 Affects many organs within seconds to minutes
after allergen exposure
 Not common
 Fatal

s/s
 Generalized pruritus and urticaria
 Erythema and angioedema
 Bronchoconstriction, mucosal edema and
excess mucus production
 Wheezes , crackles
 Anaphylactic shock

 Vital signs should be monitored closely because patients
can quickly progress to circulatory and/or respiratory
failure.
 Tachycardia may precede hypotension.
 Patients who are hypotensive may have reflex
tachycardia, but bradycardia can also occur in 5%.
 Patients may have urticaria, angioedema, or both.
 Angioedema of the airway and throat can result in
respiratory failure or asphyxiation; therefore, this
dangerous occurrence must be closely monitored.
 Patients may be wheezing during the respiratory
examination, which is secondary to bronchoconstriction.
 Confusion and alteration of mental status can occur.

 Establish and maintain airway
 High fowlers position
 Apply tourniquet immediately proximal to the
allergen point of entry when possible
 O2 by mask
 Assess the level of consciousness and vital
signs.

 Administer medications as ordered
 Epinephrine 0.3-.05ml subq
 Antihistamines – diphenhydramine IM or IV
 Aminophylline – theophylline IV for severe
bronchospasm
 Corticosteriods – hydrocortisone, solumedrol IV
 B2 agonists nebulization – Salbutamol, terbutaline,

 Administer epinephrine immediately
 Start intravenous fluids: Plain NSS or LR
 should be administered rapidly and as blood pressure
and overall fluid status warrant.
 Consider other vasopressors (eg, dopamine) if
hypotension does not respond to the above
measures.
 Norepinephrine may be used if dopamine is not
effective.

 isoproterenol should not be used
 because it is a peripheral vasodilator.
 Patients with beta-adrenergic blockade may be
particularly difficult to treat.
 They have both chronotropic and inotropic cardiac
suppression and may not respond to the above
treatments.
 Glucagon has positive inotropic and chronotropic
effects and is the drug of choice in these cases.
 Atropine can also be used but will only be effective in
treating bradycardia.

 H1- and H2-receptor blockers
 can be helpful in alleviating hypotension, pruritus,
urticaria, rhinorrhea, and other symptoms.
 Cimetidine, when combined with any of several H1
antihistamines, has been demonstrated to block
histamine-induced hypotension.
 Use albuterol nebulizers if needed.
 Administer a corticosteroid, which is believed to
help prevent or control the late-phase reaction.

Late phase reactions
 Transfer the patient to the hospital for further
observation and care.
 Late phase reactions
 can occur 4-6 hours after the initial reaction
 can be as severe as or worse than the original
reaction.
 In some cases, can occur up to 36 hours later.
 Education of the patient and observation is, therefore,
important.
http://emedicine.medscape.com/article/136217-treatment#showall

Prevention
 Avoid the triggering allergen as much as
possible.
 Patients should be given a prescription for at
least 2 autoinjectable epinephrine doses (eg, 2
EpiPens or 1 Twinject) and instructed in their
proper use. Importantly, patients must carry
them at all times.
 Patients can also be instructed to carry both an
H1 and an H2 antihistamine with them.

 Patients must wear a Medic Alert type of
bracelet to alert emergency responders to the
possibility of anaphylaxis.
 Patients should be taught what measures to take
in case of a future anaphylactic reaction
 e.g., immediately administer epinephrine and take the
antihistamine,
 call emergency services (eg, 911),
 or go to the nearest emergency department (even if
feeling better after the epinephrine).

 Specific allergen immunotherapy is highly
effective in preventing anaphylaxis
from hymenoptera stings and should always be
considered for patients who have experienced a
systemic reaction after an insect sting.

http://emedicine.medscape.com/article/136217-treatment#showall

Anaphylactoid reactions
 Non–IgE-mediated mast cell and basophil degranulation
can occur from a variety of substances.
 Although the mechanisms are different, the clinical
manifestations can appear the same.
 Causes can include
 radiocontrast dye, opiates, and vancomycin (eg, red man syndrome).

Anaphylactoid reactions
Mgmt
 glucocorticosteroids and both H1 and H2
antihistamines
 Pretreatment prior to exposure to iodinated radiocontrast dye
 this, together with the use of low-osmolal nonionic dye, reduces the risk of a repeat
reaction to approximately 1%.

 Aspirin and nonsteroidal anti-inflammatory drugs
(NSAIDs)
 can also cause reactions by causing release of leukotrienes
 Patients susceptible to this syndrome can develop acute asthma
exacerbation, nasal congestion, urticaria, or angioedema after
ingestion.

 Protein found in processed natural latex rubber
products

 Avoid products containing latex (surgical gloves,
tubings, condoms etc.)
 Other interventions similar to hypersensitivity
reactions

 Use synthetic substances that do
not contain latex protein
 ElastyLite gloves; other tubings,
etc

GI allergies s/s
 Patients may report nausea, vomiting,
abdominal cramping, and diarrhea after
ingestion of the offending food.
 Note that other mechanisms (eg, lactose
intolerance) commonly cause these symptoms.
 Eosinophilic esophagitis and gastritis are newly
recognized syndromes that may be allergic in
nature.

Type II:
Cytotoxic hypersensitivity

Type II. Cytotoxic Type
 Body makes special autoantibodies directed
against self-cells (antigens present on the
surface of cells or other tissue components)
 antigen:
 1. may be intrinsic to the cell membrane
 2. may take the form of an exogenous antigen
adsorbed on the cell surface.
 hypersensitivity results from the binding of
antibodies to normal or altered cell-surface
antigens

Type II examples
1. Transfusion reactions
 cells from an incompatible donor react w/ the host’s antibody
2. Erythroblastosis fetalis
 there is an antigenic difference between the mother & the fetus,
and antibodies (IgG) cross the placenta & cause destruction of
fetal red cells.
3. Autoimmune hemolytic anemia, agranulocytosis,
throbocytopenia
 individuals produce antibodies to their own blood cells, w/c are
then destroyed.
 4. Drug reactions
 antibodies are produced that react w/ the drug.

Type II hypersensitivity – immune-mediated
destruction of red blood cells

Drug (p=penicillin)
modified red blood cells
induce the production of
antibodies, because the
bound drug makes them
look foreign to the
immune system. When
these antibodies are
bound to them, the red
blood cells are more
susceptible to lysis or
phagocytosis. Onset is
dependent on the
presence of specific
antibodies.

Maternal antibody formation
preceding sensitization of the
fetus to Rh antigen.

 Discontinue the offending agent
 Plasmapheresis
 Filtration of the plasma to remove specific substances
like autoantibodies
 Symptomatic Treatment

Rh incompatibility
 Rh incompatibility occurs when the mother's
blood type is Rh negative and her fetus' blood
type is Rh positive.

 If some of the fetus' blood passes into the
mother's blood stream, her body will produce
antibodies in response.

 these antibodies could pass back through the
placenta and harm the fetus' red blood cells,
causing mild to serious anemia in the fetus.
http://www.nationwidechildrens.org/rh-incompatibility

Symptoms
 Rh incompatibility can cause symptoms ranging
from very mild to deadly.
 In its mildest form, Rh incompatibility causes the
destruction of red blood cells.
 After birth, the infant may have:
 Yellowing of the skin and whites of the eyes
(jaundice)
 Low muscle tone (hypotonia) and lethargy

Complications
 Possible complications include:
 Brain damage due to high levels of bilirubin
(kernicterus)
 Fluid buildup and swelling in the baby (hydrops
fetalis)
 Problems with mental function, movement, hearing,
speech, and seizures

Signs and tests
 polyhydramnios
 A positive direct Coombs test result
 Higher-than-normal levels of bilirubin in the
baby's umbilical cord blood
 Signs of red blood cell destruction in the infant's
blood

Treatment
 Because Rh incompatibility is preventable with
the use of RhoGAM, prevention remains the
best treatment.
 Treatment of an infant who is already affected
depends on the severity of the condition.
 Infants with mild Rh incompatibility may be
treated with:
 Feeding and fluids (hydration)
 Phototherapy using bilirubin lights

Prevention
 Rh incompatibility is almost completely preventable.
 Rh-negative mothers should be followed closely by their
obstetricians during pregnancy.
 Special immune globulins, called RhoGAM, are now
used to prevent RH incompatibility in mothers who are
Rh-negative.
 If the father of the infant is Rh-positive or if his blood type
cannot be confirmed, the mother is given an injection of
RhoGAM during the second trimester. If the baby is Rh-
positive, the mother will get a second injection within a
few days after delivery.

Prevention
 These injections prevent the development of
antibodies against Rh-positive blood. However,
women with Rh-negative blood type must
receive injections:
 During every pregnancy
 If they have a miscarriage or abortion
 After prenatal tests such as amniocentesis and chorionic villus
biopsy
 After injury to the abdomen during pregnancy

http://www.ncbi.nlm.nih.gov/pubmedhealth/
PMH0002567/

Symptoms
 The following are symptoms of ABO
incompatible transfusion reactions:
 Back pain
 Hematuria
 Feeling of "impending doom"
 Fever
 jaundice

Signs and tests
 The health care provider will perform a physical
exam. Blood tests will usually show:
 Increased Bilirubin level
 CBC shows damaged to red blood cells
or anemia
 The patient's and donor's blood are not
compatible

Treatment
 Treatment may include:
 Antihistamines
 Steroids
 IVF
 Vasopressors

http://www.ncbi.nlm.nih.gov/pubmedhealth/
PMH0002283/

Expectations (prognosis)
 ABO incompatibility can be a very serious
problem that can even result in death. With the
right treatment, a full recovery is likely.

 Complications
 Kidney failure
 Hypotension
 Death

Type III: Immune complex-
mediated hypersensitivity

Type III hypersensitivity

 Involve reactions against soluble antigens
circulating in serum.
 Usually involve IgM, IgG antibodies.
 Antibody-Antigen immune complexes are
deposited in organs, activate complement, and
cause inflammatory damage.
 Glomerulonephritis: Inflammatory kidney damage.
 Occurs with slightly high antigen-antibody ratio is
present.

Type III hypersensitivity – immune complex
formation and deposition

Immune complexes
activate complement
Immune complexes of
(green dots- C3a, C4a, Inflammation and
antigen (red dots) and
and C5a), and mast cells edema occur, and
antibody form in
(yellow cell) degranulate. organ is damaged
target organ

134

 Every time an antibody binds to antigen, an
immune complex is formed.
 Under normal conditions complexes are bound
by complement to RBCs and then eliminated by
phagocytes.
 Complement may also weaken the antibody-
antigen bonds thereby re-dissolving the
complexes.

 In Type III hypersensitivity, immune complexes are not
cleared out and they become deposited in tissues.
 Immune-complex disease may result from:
 a) persistent low-grade infection, as in malaria and
viral hepatitis;
 b) autoimmunity, as in rheumatoid arthritis and
systemic lupus erythematosis; and
 c) inhaled antigens, as in farmer’s lung and pigeon
fancier’s lung where there is repeated exposure to mold
or pigeon antigen.

 In Type III hypersensitivity, the antibody involved is primarily IgG.
 In the diagram, the presence of immune complexes activates
complement (C3a, C4a and C5a are the names given to some of the
components of complement), leading to degranulation of mast cells.
 The products of mast cell degranulation cause blood vessels to
become more permeable.
 This allows immune complexes to be deposited in the walls of blood
vessels.
 Platelets aggregate in the vicinity of the deposits.
 Neutrophils are attracted to the site but are unable to ingest the
complexes because they are bound to the vessel wall.
 The neutrophils release lysosomal enzymes into the area, causing
further damage to the vessel wall.


Type III hypersensitivity – immune complex
formation and deposition

 In sensitized individuals, allergen (antigen)
combined with antibody leads to the formation of
immune complexes, which activate complement
and the inflammatory response.
 The location of the inflammation depends on the
location of the antigen - inhaled, under skin,
systemic.
 Onset is usually within 2-6 hours.

138

 induced by antigen-antibody complexes having the
capacity to activate a variety of serum mediators,
principally the complement system.
 Generalized
 if immune complexes are formed in the circulation & are
deposited in many organ
 Localized to particular organs:
 kidney (glomerulonephritis), joints (arthritis),
 small blood vessels of the skin if the complexes are formed and
deposited locally (local Arthus reaction)

Arthus reaction
• A dermal inflammatory
reaction produced under
conditions of antibody
excess, when a second
injection of antigen
produces intravascular
antigen-antibody
complexes which bind
complement, causing cell
clumping, endothelial
damage, and
vascular necrosis

 Note: wherever complexes deposit, the tissue
damage is the same: complement cascade and the
elaboration of biologically active fragments.

 Rheumatoid arthritis
 Systemic Lupus Erythematosus
 Serum sickness

Serum sickness
 a condition that may develop when a patient is
injected with a large amount of e.g. antitoxin that
was produced in an animal or other drugs
 After about 10 days, anti-antitoxin antibodies
react with the antitoxin forming immune
complexes that deposit in tissues, walls of the
blood vessels, skin, joints, kidney
 Most common cause is penicillin and animal
serum antitoxins

s/s
 Fever
 Arthralgia
 Rash
 Lymphadenopathy
 Malaise
 Polyarthritis and nephritis

 Usually Self limiting
 Symptomatic treatment
 Aspirin for pain
 Antihistimines for pruritus
 Steroids - prednisone

Type IV: Delayed
Hypersensitivity

Type IV hypersensitivity
 the only type that is not antibody-mediated.
 contact hypersensitivity (poison ivy, reactions to
metals in jewelry);
 tuberculin-type hypersensitivity (the tuberculosis skin
test);
 granulomatous hypersensitivity (leprosy, tuberculosis,
schistosomiasis and Crohn’s disease).

 It is called delayed because its onset may vary;
 Occurs hours to days
 the length of the delay varies from 72 hours in contact
and tuberculin-type to 21-28 days in granulomatous
hypersensitivity.
 Self limiting

Type IV. Cell-Mediated
 Initiated by specifically sensitized T lymphocytes
which respond to an antigen by producing and
releasing certain lymphokines and they recruit,
retain and activate macrophages to destroy the
antigen
 Antibodies and complement are not involved

Type IV hypersensitivity – delayed-type or contact
T cells (blue cells)
that recognize
Antigen (red dots) antigen are Inflammatory
are processed by activated and response causes
local APCs release cytokines tissue injury.

155

Type IV hypersensitivity – delayed-type or contact
T cells (blue cells)
that recognize
Antigen (red dots) antigen are Inflammatory
are processed by activated and response causes
local APCs release cytokines tissue injury.

Antigen is presented by APCs to antigen-specific memory T cells that
become activated and produce chemicals that cause inflammatory
cells to move into the area, leading to tissue injury. Inflammation by 2-
6 hours; peaks by 24-48 hours.
156

Type IV hypersensitivity
 antigen presented by APCs activates antigen-
specific memory T cells (which have been
sensitized by prior exposure),
 causing them to release cytokines that activate
and attract other T cells and phagocytic cells to
the area.
 Where the source of antigen is at the skin
surface, the APC migrates from the dermis,
through lymphatic vessels to a lymph node in
order to present antigen to a T cell.

 In the TB skin test, a small amount of soluble
antigen (tuberculin) is injected into the skin.
 The T cells that are activated by the antigen
secrete cytokines that draw other cells to the
site.
 Within four hours, neutrophils have arrived,
followed by an influx of monocytes and T cells at
about 12 hours.
 The peak of activity is at about 48-72 hours, at
which point the area has become red and
swollen.

1. Tuberculin reaction
- the best known example
of delayed-type
hypersensitivity
- produced by
intracutaneous injection of
tuberculin
- In previously sensitized
individual: reddening and
induration of the site(8-12
hours), peaks in 24-72 hours,
and thereafter slowly subside.

2. Transplant rejection
3. Contact dermatitis
4. Poison Ivy skin rashes
5. Local response to insect stings

Patch Testing
• Used to identify the allergen
• Skin contact with substances
to which the client is
potentially allergic
• Contact with a specific
allergen results in a delayed
reaction that develops in 48-
96 hours
• Substances applied under
occlusive tapes
• Localized erythema, blister,
swelling

 Removal of the offending antigen
 Monitor reaction site and sites distal to the
reaction for circulation adequacy
 Antihistamines – minimal benefit
 Steroids

Type V. Stimulatory Reactions
• Inappropriate stimulation of
a normal cell surface
receptor by an autoantibody,
resulting in an continuous
“turned-on” state for the cell
• Example – Graves Disease
– An autoantibody binds to TSH
receptor sites in the thyroid
gland stimulating it to produce
thyroid hormones continually

 If one organ is involved like in Graves disease
,surgical removal or radiation can be done
 If more than one organ is involved then
immunosuppresion is warranted

THE IMMUNE SYSTEM IN
HEALTH AND DISEASE

How does your everyday life affect
your immune system?

167

Exercise and stress

 exercise has been shown to boost the immune response
 moderate exercise increases the immune response in all age
groups
 intensive exercise can stress the immune system

 lack of sleep and exhaustion decrease immune function

 psychological stress has also been found to decrease
immune function

168

Diet

 a well-balanced diet is essential for good immune
system health
 fats are very important in the production of WBCs, cytokines
and natural killer cells
 selenium, zinc, and copper are required in small amounts,
which you get if you eat a balanced diet
 vitamin E has been shown to boost antibody production in
the elderly
 vitamin B6 aids in antibody synthesis

 but mega-dosing can be harmful, too!
169

Environment
Exposure to certain things in their environment may
activate the immune systems of some people

• Chemicals • Viruses
– dioxin
– pesticides
– solvents
• Bacteria
• Sunlight

• Medication • Food

170

Gender and the immune system

 women respond to antigens more strongly than men

 estrogen may affect the development or function of
immune cells

 may explain why more women develop autoimmune
diseases

171

Sarcoid - close-up of the skin
lesions
• Sarcoid - close-up of the
skin lesions: 20 to 25
percent of individuals with
sarcoidosis have skin
manifestations as seen in
this picture.
• The extent of the skin
manifestations is difficult to
predict, but the most
common are red papules
that are translucent as seen
here.

Erythema nodosum
associated with sarcoidosis
• This picture shows reddish-
purple, hard (indurated),
painful nodules (Erythema
nodosum) that occur most
commonly on the shins. These
lesions may be anywhere on
the body and may be
associated with tuberculosis
(TB), sarcoidosis,
coccidioidomycosis, systemic
lupus erythematosis (SLE),
fungal infections, or in
response to medications

Sarcoidosis - close-up
• Typical sarcoid
lesions consist of red,
raised lesions
(papules) and
patches (plaques)
with minimal
surrounding skin
change.

Sarcoidosis on the elbow
• These lesions of
sarcoidosis are
located on the elbow
and are red, elevated
patches (plaques).
The cause of
sarcoidosis remains
unknown.

Sarcoidosis on the nose and
forehead
• These are sarcoid
lesions on the face.
These lesions often
appear in scars, as is
seen in this
photograph.

•http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001140/

Sarcoid, stage I - chest x-ray
• Sarcoid is primarily a
lung (pulmonary)
disease. In the early
stages, a chest film
may show
enlargement of lymph
nodes in the center of
the chest near the
heart (mediastinum).

Sarcoid, stage II - chest x-ray
• Sarcoid causes
damage to the lung
tissue that heals by
scarring. The film
shows a diffuse milky
and granular
appearance in the
normally dark lung
areas. This individual
has marked decrease
in lung function.

Sarcoid, stage IV - chest x-ray
• This film shows
advanced sarcoid,
scarring of the lungs
(the light streaking),
and cavity formation
(the dark areas in the
upper right side of the
picture).

Hypersensitivity reactions

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